Effects of barbiturates in rats tolerant to delta 9-tetrahydrocannabinol.

Rats, whose behavior was maintained under a multiple fixed-ratio fixed-interval schedule of food presentation, were given delta 9-tetrahydrocannabinol (delta 9-THC), pentobarbital, barbital, and d-amphetamine before, during and after chronic delta 9-THC administration. Low doses of the barbiturates and d-amphetamine increased rates of responding, especially under the fixed-interval component. Higher doses of all four drugs decreased rates of responding under both schedule components. Tolerance developed to the rate-decreasing effects of delta 9-THC and there was cross tolerance to the rate-decreasing effects of pentobarbital and to a lesser extent barbital, but not to the rate-decreasing effects of d-amphetamine. During chronic delta 9-THC administration, rate-increasing effects of pentobarbital and barbital continued to occur, but the rate-increasing effects of d-amphetamine were attenuated. A second group of rats whose behavior was maintained under a variable-interval schedule of food presentation were given delta 9-THC and barbital before and during chronic barbital administration. Low doses of barbital increased rates of responding and higher doses of both drugs decreased rates. Tolerance developed to the rate-decreasing effects of barbital and there was cross tolerance to delta 9-THC. No tolerance developed to the rate-increasing effects of barbital. Thus, there is cross tolerance between barbiturates and delta 9-THC for rate-decreasing effects on schedule-controlled behavior, but neither tolerance nor cross tolerance occurs for rate-increasing effects.